250
acid) [p(NIPAAm-co-AAc] and crosslinked with a peptide (Li et al. 2006 ). These
are two examples of 2D and 3D polymeric scaffolds with controlled and well-
defined properties that are being developed as platforms for in vitro cell studies to
investigate the interactions of cells and materials. While a 3D network mimics
closely the native environment of the cell, a 2D scaffold allows more control over
surface properties such as topography and roughness.
13.2.2.1 Surface Topography
Controlling the nano and micro scale topography of a polymeric substrate has a
direct effect on the cell behavior (Murphy et al. 2014b). Also, generating well-
defined patterns in these substrates has the potential to produce functional custom-
ised tissues for applications in regenerative medicine. In a study by Kim et al.
( 2010 ) the adhesion of human adipose-derived stem cells (hASCs) is shown to be
favourable on micro-patterned surfaces of poly(lactic-co-glycolic acid) (PLGA) as
opposed to unpatterned surfaces. The long-term self-renewal (>3 weeks) of mouse
embryonic stem cells (mESCs) cultured on 2-hydroxyethyl methacrylate-co-
ethylene dimethacrylate (HEMA-EDMA) substrates is shown to be dependent on
the surface roughness (Jaggy et al. 2015 ). Substrates with a hierarchical topography
at both nano- and microscale (large agglomerates up to 9 μm in height with an aver-
age surface roughness (Sa) of 919 ± 22 nm) supported the long-term maintenance
of mESCs. On the contrary, culturing of mESCs on either smooth (Sa = 2 ± 0.4 nm)
or nano rough surfaces (Sa = 68 ± 30 nm) led to their fast differentiation. McMurray
et al. ( 2011 ) identified a nanostructured polycaprolactone surface that retains a
stem cell phenotype and maintains stem cell growth over 8 weeks. In a 3D configu-
ration, the adhesion and expansion of hESCs was tested on electrospun nanofibers
mats fabricated from three synthetic FDA approved polymers: (i) poly-ɛ-
caprolactone (PCL), (ii) poly-L-lactic acid (PLLA) and (iii) poly lactic-co-glycolic
acid (PLGA) (Kumar et al. 2015 ). The study reported three important factors that
can modulate the colony size of stem cells: chemical nature of the polymer back-
bone, the diameter size of the fibre and the fibre orientation. PCL polymer pre-
sented as the most supportive substrate for hESCs self-renewal (see Fig. 13.2).
Smaller diameter nanofibrous substrates (280 ± 122 nm) supported a significantly
greater number of hESC colonies, relative to their larger diameter counterparts
(521 ± 195 nm). Aligned nanofibrous substrates were found to be more suited than
their random counterparts. With the advent of technology, various fabrication tools
are available for researchers to produce controlled micro or nanoscale features on
polymeric surfaces facilitating adhesion and proliferation of cells. Examples
include photolithography, printing techniques, self-assembly of block copolymers
and instability-induced patterning (Nie and Kumacheva 2008 ). These techniques
allow patterning of the polymeric surface at different length scales and hence more
control over directing the stem cell fate.
D. Mawad et al.